Richard B. Weinberg, MD
Professor, Internal Medicine (Gastroenterology)
Professor, Physiology & Pharmacology
Associate in Biochemistry
Associate Director, General Clinical Research Center
To contact Dr. Weinberg:
Tel: (336) 713-7313
Fax: (336) 713-7322
Interests:
- Clinical: General Gastroenterology; Nutrition
- Teaching: Gastroenterology; Nutrition; Doctor-Patient Relationships
- Research: Biophysics of Protein-Lipid Interactions; Lipoprotein Metabolism; Role of Apo A4 in Human Lipid Metabolism; Diet-Gene Interactions
Education:
- Undergraduate: Harvard University: AB, 1971
- Postgraduate: Johns Hopkins University: MD, 1975
- Residency: University of Chicago Hospitals and Clinics, 1975-1978
- Fellowship: University of Chicago Hospitals and Clinics, 1978-1981
Board Certifications:
- American Board of Internal Medicine, 1978
- American Board of Internal Medicine/Gastroenterology, 1981
Current Research:
Research in our laboratory is focused upon the elucidation of the structure and function of human apolipoprotein A-IV (apo A-IV), a 46 kD intestinal lipid-binding protein that is synthesized by the small intestine during fat absorption. We have demonstrated that apo A-IV possesses dynamic interfacial properties that are optimal for stabilizing surface tension and molecular packing at lipid/aqueous interfaces. We propose that by facilitating expansion of nascent chylomicrons, apo A-IV can modulate the efficiency of intestinal lipid absorption.
We utilize a broad array of biophysical techniques to study the structure-function relationships of apo A-IV: UV, fluorescence, and circular dichroism spectroscopy to allow us to probe the effect of naturally occurring and recombinant apo A-IV mutations on its molecular structure, whereas sophisticated surface chemistry techniques, such as a Langmuir surface balance and an automated oil-drop tensiometry enable us to examine how structural alterations in apo A-IV affect its interfacial behavior and ability to stabilize expanding lipid surfaces.
A related second arm of our research examines the functional genomics of apo A-IV. We use human apo A-IV transgenic and knock-out mice to examine the impact of apo A-IV expression on the efficiency of intestinal lipid absorption. We also study the interaction of diet and human genetic apo A-IV polymorphisms on dietary lipid absorption, lipid metabolism, and lactation in the General Clinical Research Center.
We expect that these studies will provide insight into the specific role of apo A-IV in the the complex process of intestinal lipid absorption, and the impact of apo A-IV genetic polymorphisms on the risk of atherosclerotic cardiovascular disease and obesity. This research has been continuously supported by the NIH National Heart, Lung, and Blood Institute for over 20 years; our current funding cycle extends through 2011. Opportunities exist for both pre- and post-doctoral study.
Recent Publications:
Beckstead JA, Wong K, Gupta V, Wan CP, Cook VR, Weinberg RB, Weers PM, Ryan RO. The C terminus of apolipoprotein A-V modulates lipid-binding activity. J Biol Chem. 2007 May 25;282(21):15484-9.
Wong WM, Gerry AB, Putt W, Roberts JL, Weinberg RB, Humphries SE, Leake DS, Talmud PJ. Common variants of apolipoprotein A-IV differ in their ability to inhibit low density lipoprotein oxidation. Atherosclerosis. 2007 Jun;192(2):266-74.
Ledford AS, Weinberg RB, Cook VR, Hantgan RR, Shelness GS. Self-association and lipid binding properties of the lipoprotein initiating domain of apolipoprotein B. J Biol Chem. 2006 Mar 31;281(13):8871-6.
Lu S, Yao Y, Cheng X, Mitchell S, Leng S, Meng S, Gallagher JW, Shelness GS, Morris GS, Mahan J, Frase S, Mansbach CM, Weinberg RB, Black DD. Overexpression of apolipoprotein A-IV enhances lipid secretion in IPEC-1 cells by increasing chylomicron size. J Biol Chem. 2006 Feb 10;281(6):3473-83.
Pearson K, Tubb MR, Tanaka M, Zhang XQ, Tso P, Weinberg RB, Davidson WS. Specific sequences in the N and C termini of apolipoprotein A-IV modulate its conformation and lipid association. J Biol Chem. 2005 Nov 18;280(46):38576-82.
Gallagher JW, Weinberg RB, Shelness GS. ApoA-IV tagged with the ER retention signal KDEL perturbs the intracellular trafficking and secretion of apoB. J Lipid Res. 2004 Oct;45(10):1826-34.
Shelness GS, Hou L, Ledford AS, Parks JS, Weinberg RB. Identification of the lipoprotein initiating domain of apolipoprotein B. J Biol Chem. 2003 Nov 7;278(45):44702-7.
Weinberg RB, Cook VR, Beckstead JA, Martin DD, Gallagher JW, Shelness GS, Ryan RO. Structure and interfacial properties of human apolipoprotein A-V. J Biol Chem. 2003 Sep 5;278(36):34438-44.
Weinberg RB, Anderson RA, Cook VR, Emmanuel F, Denefle P, Tall AR, Steinmetz A. Interfacial exclusion pressure determines the ability of apolipoprotein A-IV truncation mutants to activate cholesterol ester transfer protein. J Biol Chem. 2002 Jun 14;277(24):21549-53.